Expert Analysis

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Atrial fibrillation (AF) increases the risk of stroke, and effective anticoagulation mitigates this risk. Increased bleeding risk and subtherapeutic anticoagulation subvert the effectiveness of anticoagulation. These factors are especially challenging in the elderly population, in whom the bleeding risks are higher than usual. Left atrial appendage (LAA) exclusion is emerging as an alternative to therapeutic anticoagulation in AF patients. Most recently, the US Food and Drug Administration (FDA) approved WATCHMAN, which is a percutaneously implantable LAA occlusion device.

WATCHMAN is a parachute-shaped device made from nitinol framework and covered by a polytetrafluoroethylene membrane. This device is implanted in the LAA using a percutaneous approach under TEE and fluoroscopic guidance. Following the implantation of the WD, flow into the LAA is excluded and the substrate for thrombus formation in the LAA is excluded from the systemic circulation.

Multiple studies have clearly established that WATCHMAN has comparable efficacy to warfarin in mitigating stroke risk in AF. The WATCHMAN Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation (PROTECT-AF) study was a multicenter, randomized clinical trial that randomized patients in a 2:1 ratio to WATCHMAN implantation and warfarin groups.1 They included AF patients with a CHADS2 score of ≥ 1. The mean age of the study population was 71.7 ± 8.2 years in the WATCHMAN group and 72.7 ± 9.2 years in the warfarin group. Elderly adults (≥ 75 years) comprised 41% and 47% of the WATCHMAN device and warfarin groups, respectively. Over a follow-up period of 3.8 years and aggregate patient follow-up of 2621 years, the WATCHMAN device met the criteria for both noninferiority and superiority for the primary efficacy outcome of stroke, systemic embolization, and cardiovascular death. The primary efficacy endpoints occurred in 8.4% and 13.9% of the patients in the WATCHMAN device and warfarin groups, respectively. The hazard ratio (HR) was 0.61 (95% confidence interval [CI] 0.38–0.97) in favor of the device and met the posterior probability for noninferiority (99%) and superiority (96%) on Bayesian analyses. For the individual outcome of stroke, the rate ratio (RR) was 0.68 (95% CI 0.42–1.37), this met the criteria for noninferiority (99%) but not superiority. There were far fewer hemorrhagic (RR 0.15, 95% CI 0.03–0.49) and disabling strokes (RR 0.37, 95% CI 0.15–1.0) in the WATCHMAN device group and met the criteria for superiority. The WATCHMAN device group in elderly patients also had a trend towards lower primary efficacy events (HR 0.63, 95% CI 0.35–1.14). The primary safety events were similar between the two groups (HR 1.21, 95% CI 0.78–0.94), and this met the criteria for noninferiority (98% posterior probability). The slightly higher event rate in the WATCHMAN device group was driven by the incidence of periprocedural complications of periprocedural stroke, pericardial effusions, and bleeding events.

The higher periprocedural events were attributed to the learning curve of the operators and, subsequently, a non-randomized study; Continued Access Protocol (CAP) was done to assess the safety of the WATCHMAN device.2 This study involved 460 patients at 26 centers, and the mean age of the study participants was 74 ± 8 years. In this study, the procedure-related complications decreased to 3.7% compared to 7.7% in the PROTECT-AF study. The incidence of pericardial effusion also decreased to 2.2% from a high of 5% in the PROTECT-AF study. The risk of periprocedural stroke also decreased to 0% in the CAP registry. This study further established the safety of implantation of the WATCHMAN device.

Further evidence of effectiveness of the WATCHMAN device was demonstrated in the Watchman LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy (PREVAIL) study.3 In this multicenter, randomized study, AF patients who had a CHADS2 score of 2 or a score of 1 and another risk factor, such as female age ≥ 75 years, baseline ejection fraction ≥ 30% but < 35%, age 65 to 74 years with either diabetes or coronary disease, and age ≥ 65 years with congestive heart failure, were randomized to WATCHMAN device or warfarin groups. A total of 407 patients were enrolled, 269 in the WATCHMAN device group and 138 in the warfarin groups. The mean age was 74.0 ± 7.4 years in the WATCHMAN device group and 74.9 ± 7.2 years in the control group. Elderly patients constituted 52% and 56.5% of the WATCHMAN device and warfarin groups, respectively. After a mean follow-up period of 18 months, the primary efficacy endpoint (stroke, systemic embolism, and death) was not different between the two groups. The RR was 1.07 (95% CI 0.57–1.89); although there was no statistical difference between the two groups for this endpoint, it did not meet the predefined criteria for noninferiority. However, the noninferiority criterion was met for the endpoint of late ischemia (stroke or systemic embolism after 7 days of randomization). The incidence of procedural complications was also significantly lower in the PREVAIL study compared to the PROTECT-AF trial.

Most recently, patient-level meta-analysis of the WATCHMAN trials (PROTECT-AF and PREVAIL) and their continued access registries (Continued Access to PROTECT [CAP] and Continued Access to PREVAIL [CAP2]) were published.4 This meta-analysis included 2,406 patients with 5,391 patient years of follow-up. The HR for efficacy (stroke, embolism, and death) was 0.79 (p = 0.22) in favor of WATCHMAN. The risks of hemorrhagic stroke, cardiovascular death, and non-procedural related death were all significantly lower in the patients treated with WATCHMAN. There was a trend towards higher risk of ischemic stroke in the WATCHMAN device group (HR 1.95, p = 0.05), although this did not reach statistical significance. All-cause mortality was similar in both the groups. The risk of primary efficacy was not different between the WATCHMAN device and warfarin groups. There have not been any clinical trials exclusively studying the safety and efficacy of the WATCHMAN device in the elderly patients about 40–60% of the patients included in these trials were > 75 years.

This device has been approved by the FDA for LAA exclusion for use in patients with non-valvular AF and increased risk for stroke and systemic embolism, and eligible for anticoagulation with warfarin but have an appropriate rationale for seeking non-pharmacological alternative to anticoagulation. The current American College of Cardiology (ACC)/American Heart Association (AHA) guidelines do not specify the indications for catheter-based LAA exclusion techniques.5 The 2012 European Society of Cardiology focused update on AF recommended a Class IIb indication for catheter-based LAA exclusion techniques.6 Both of these guidelines were written prior to the FDA approval of the WATCHMAN device. The European Heart Rhythm Association/European Association of Percutaneous Cardiovascular Interventions issued a consensus statement on catheter-based LAA occlusion in 2014.7 According to this statement LAA exclusion had the clearest indication in patients who had absolute contraindication to anticoagulation and possible indication in patients with increased risk for bleeding.7

Elderly patients with AF form the high-risk cohort for both bleeding and stroke. Because of the higher risk of bleeding, anticoagulation therapy is not aggressively pursued and remains underutilized in elderly AF patients.8 Frailty is another factor to consider in elderly patients. Frail patients are also at increased risk of stroke and bleeding.9 Anticoagulation is underutilized in patients with high frailty index and also in those with increased risk of falls.10 Therefore, this cohort of patients may be eligible and may benefit from LAA occlusion with the WATCHMAN device. Implantation of this device would obviate the need for oral anticoagulation and also mitigate stroke risk. However, it has to be remembered that short-term oral anticoagulation was used in the previously mentioned clinical trials until complete sealing of the LAA was observed. Therefore, this may be challenging in patients with absolute contraindications to anticoagulation. A smaller, non-randomized, prospective study demonstrated the feasibility of using Watchman with dual antiplatelet therapy (aspirin and clopidogrel) without the need for short-term anticoagulation therapy in patients with absolute contraindications to oral anticoagulation, which may be an option. The implantation of the WATCHMAN device is not without complications and is not suited for all patients given the size limitations of the device, and appropriate preprocedural planning and multimodality imaging is needed to ascertain eligibility.

In the authors’ opinion, anticoagulation therapy with warfarin and the newer oral anticoagulants have been demonstrated to be efficacious in decreasing stroke risk and should be tried as the first option in eligible patients. In those patients in whom oral anticoagulation is associated with increased risk, and obvious contraindications to anticoagulation may be considered for LAA exclusion with the WD. Transcatheter exclusion of the LAA is a relatively new frontier and the types of devices, indications, and operator experiences continue to evolve. As these devices become increasingly used, safety and long-term efficacy of these devices need to be ascertained in geriatric patients.

January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2014;64:2246-80.

Camm AJ, Lip GY, De Caterina R, et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J 2012;33:2719-47.